Predicting the effect of temporal variations in Po2 on tumor radiosensitivity

Purpose: Tumor hypoxia is associated with less effective radiation-mediated cell killing, increased metastatic potential, and poorer prognosis. Transient variations in hypoxia, with characteristic periodicity on the order of 1 to 10 min, have been observed in animal models. This article explores the effect of these temporal variations in Po-2 on the oxygen enhancement ratio, effective radiation dose to the tumor, and tumor control probability. Methods and Materials: Po-2 over a 50-60 min period was determined at multiple sites in rat fibrosarcomas, 9L gliomas, and R3230Ac mammary adenocarcinomas. Using a correlation derived from the data of Elkind et al. (1965), Po-2 data are converted into oxygen enhancement ratios (OERs.) A tumor is assumed to consist of 10(3)-10(4) independent oxygenation subvolumes, each with a randomly chosen starting point on the OER-time curve. The effect of temporal variations in OER is examined for three cases: conventionally fractionated external beam radiotherapy (EBRT), stereotactic radiosurgery (SRS) and intraoperative radiotherapy (IORT). The oxygen effective dose (OED) for a subvolume is calculated from the dose to that subvolume modified by the OER. In turn, the distribution of OED for a tumor is analyzed for each treatment case and representative tumor control probabilities (TCPs) calculated. Results: Oxygen enhancement ratio varied from 1 to 3 over the range of Po-2 measured in this study. Mean OER ranged from 1.6 to 2.6, and the variation in OER vs. time was greater with decreasing Po-2 In EBRT, the standard deviation in OED was small, <2%. In contrast, the standard deviation in OED was much higher for both SRS and IORT, typically ranging from 3 to 6%, with the greatest variation at the lowest Po(2)s. Compared with a tumor with equal mean OED and uniform Po-2, TCP was minimally poorer for either EBRT or well-oxygenated tumors. However, for both SRS and IORT, temporal variations in more hypoxic tumors can produce a significant decrease in TCP. Conclusion: Temporal variations in tumor Po-2 can produce significant variations OER, particularly at low Po-2, resulting in decreased TCP for hypofractionated treatment regimens. (C) 2004 Elsevier Inc.